The objective of this program project is an integrated multidisciplinary approach to drug design. In particular, the concept of pharmacophore will be tested in a variety of systems by systematic examination of its consequences through the active analog approach. Exhaustive innumeration of possible orientations of candidate functional groups for the pharmacophore will be examined in series of active compounds. One a pharmacophore consistent with the entire set of compouns is obtained, then it will be used to map receptor sites. Development of this approach conceptually as well as algorithmically is a primary objective. The processing through multiarray processors as a prologue to VLSI implementation. Alternative formulations of the problem by distance geometry will also be explored. This approach will be applied to isolated enzyme systems which transform steroids, or synthesize S-adenosylmethionine. Dopamine and other biogenic amines receptors will be examined to probe receptor heterogenity. The receptor-bound conformation of peptide hormones, i.e. angiotensin, thyroliberin, bradykinin and enkephalin, will be determined through the introduction synthetically of conformational constraints and their conformational analysis.